The research is designed to test, on the cellular level, a proposed mechanism for the impaired target tissue response to parathyroid hormone in the D-deficient animal. The hypothesis is (1) the hypocalcemia which occurs as a result of D-deficiency induces secondary hyperparathyroidism and (2) the resulting chronic high level of circulating parathyroid hormone subsequently alters the parathyroid hormone-sensitive adenylate cyclase system of target cells. Two cell types will be studied: (1) the isolated renal cortical tubule from rat kidney and (2) the isolated bone cell from newborn rat calvaria. Companion studies will be performed in vitro with tissue preparations from the same sources. The objectives of the research are: (1) to compare the responses of adenylate cyclase from both bone and kidney during D-deficiency (2) to ascertain whether or not the impaired parathyroid hormone-dependent adenylate cyclase activity during D-deficiency (2) to ascertain whether or not the impaired parathyroid hormone-dependent adenylate cyclase activity during D-deficiency is reflected in altered cellular c-AMP levels and parathyroid hormone responsive cell functions (3) to mimic the proposed action of parathyroid hormone in vitro by exposing the cells to chronic high levels of the hormone and (5) to directly study membrane receptors in these cells by assessing the binding of 125I-parathyroid hormone to membranes prepared from these cells.